Role for the Epidermal Growth Factor Receptor in Chemotherapy-Induced Alopecia

Kyle J. Bichsel, Navdeep Gogia, Timothy Malouff, Zachary Pena, Eric Forney, Brianna Hammiller, Patrice Watson, Laura A. Hansen

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Abstract

Treatment of cancer patients with chemotherapeutics like cyclophosphamide often causes alopecia as a result of premature and aberrant catagen. Because the epidermal growth factor receptor (EGFR) signals anagen hair follicles to enter catagen, we hypothesized that EGFR signaling may be involved in cyclophosphamide-induced alopecia. To test this hypothesis, skin-targeted Egfr mutant mice were generated by crossing floxed Egfr and Keratin 14 promoter-driven Cre recombinase mice. Cyclophosphamide treatment of control mice resulted in alopecia while Egfr mutant skin was resistant to cyclophosphamide-induced alopecia. Egfr mutant skin entered catagen normally, as indicated by dermal papilla condensation and decreased follicular proliferation, but did not progress to telogen as did Egfr wild type follicles. Egfr mutant follicles responded with less proliferation, apoptosis, and fewer p53-positive cells after cyclophosphamide. Treatment of control mice with the EGFR inhibitors erlotinib or gefitinib similarly suppressed alopecia and catagen progression by cyclophosphamide. Secondary analysis of clinical trials utilizing EGFR-targeted therapies and alopecia-inducing chemotherapy also revealed evidence for involvement of EGFR in chemotherapy-induced alopecia. Taken together, our results demonstrated the involvement of EGFR signaling in chemotherapy-induced alopecia, which will help in the design of novel therapeutic regimens to minimize chemotherapy-induced alopecia.

Original languageEnglish
Article numbere69368
JournalPLoS One
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 19 2013

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All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bichsel, K. J., Gogia, N., Malouff, T., Pena, Z., Forney, E., Hammiller, B., ... Hansen, L. A. (2013). Role for the Epidermal Growth Factor Receptor in Chemotherapy-Induced Alopecia. PLoS One, 8(7), [e69368]. https://doi.org/10.1371/journal.pone.0069368